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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林建達 | zh_TW |
| dc.contributor.advisor | Jian-Da Lin | en |
| dc.contributor.author | 趙珮安 | zh_TW |
| dc.contributor.author | Pei-An Chao | en |
| dc.date.accessioned | 2023-10-03T17:37:58Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2023-10-03 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-08-01 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90790 | - |
| dc.description.abstract | 寄生蟲感染在開發中國家是個常見疾病。最近的研究指出，原住民罹患心血管疾病的風險較低，這可能與他們腸道微生物群與腸道寄生蟲感染的協同演化有關。先前的研究表明寄生蟲感染，如多型性螺旋線蟲（Heligmosomoides polygyrus）和 鼠鞭蟲（Trichuris muris）能誘導腸道中的第二型免疫反應和調節性T細胞（Tregs）擴增。然而，腸道寄生蟲感染與心血管疾病之間的關係尚不明確。因此我們假設寄生蟲感染所引起的第二型免疫反應以及調控型T細胞能夠介導動脈粥狀硬化斑塊的復原。我們觀察到，相比於對照組，全身性的FoxP3+ CD4 T細胞及GATA3+ 輔助型T細胞在受寄生蟲感染的小鼠血液中顯著增加。對寄生蟲感染的動脈粥狀硬化小鼠進行主動脈根部切片進行了連續定量分析證實了斑塊的逆轉，而免疫組織化學染色進一步觀察到巨噬細胞含量的顯著下降。此外，在斑塊逆轉期間，我們也觀察到主動脈弓中CD4 T細胞數量的明顯增加，以及CD11b+ F4/80+ 巨噬細胞的減少。這表示在寄生蟲感染的動脈粥樣硬化小鼠中，調節性 T 細胞可能在斑塊逆轉期間浸潤至動脈粥樣硬化斑塊中。總之，我們透過誘導全身性的調控型T細胞和第二型免疫反應，提供了一種可行且新穎的治療技術，用以治療動脈粥狀硬化。 | zh_TW |
| dc.description.abstract | Helminth infection is a common disease in developing countries. Recent studies indicate that indigenous people are less likely to suffer from cardiovascular diseases, which may be correlated to their intestinal Microbiome changes coevolved with intestinal helminth infection. Previous studies showed that helminth infection, Heligmosomoides polygyrus (H. polygyrus) and Trichuris muris (T. muris), can induce type 2 immune responses and regulatory T cells (Tregs) expansion in the gut. However, the links between intestinal helminth infection and cardiovascular diseases are poorly understood. We hypothesized that Tregs or type 2 immunity induction by H. polygyrus or T. muris infection mediates atherosclerotic plaque regression. We observed systemic FOXP3+ CD4 Treg and GATA3+ T helper 2 (Th2) cells are significantly increased in the blood of H. polygyrus and T. muris infected mice than in control mice. Serial quantitative analysis of aortic root sections from H. polygyrus or T. muris infected atherosclerotic mice confirmed plaque regression, and a significant decrease of macrophage contents was observed by immunohistochemistry. Furthermore, we also observed a significant increase in the number of CD4 T cells and a decrease in CD11b+ F4/80+ macrophages in the aortic arch during plaque regression. It indicated regulatory T cells might infiltrate into atherosclerotic plaques during plaque regression in H. polygyrus or T. muris-infected atherosclerotic mice. Overall, we may provide a novel therapeutic for the resolution of atherosclerosis by helminth-induced systemic Treg and Type 2 immunity inductions. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-10-03T17:37:58Z No. of bitstreams: 0 | en |
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| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii ABSTRACT iv CONTENTS v LIST OF FIGURES x LIST OF TABLES xii LIST OF ABBREVIATION AND ACRONYM xiii Chapter 1 Introduction 1 1.1 Atherosclerosis 1 1.2 Monocyte and Macrophage in Atherosclerosis 2 1.3 T lymphocyte in Atherosclerosis 4 1.4 Regulatory T cell in Atherosclerosis 6 1.5 Type 2 Immunity 7 1.6 Helminth Infection 9 1.7 Nucleotide-binding oligomerization domain-containing protein 2 gene 11 1.8 Aim of this study 12 Chapter 2 Materials and Methods 14 2.1 Study Design 14 2.2 Materials 15 2.2.1 Reagent or Resource 15 2.2.2 Equipment and Apparatus 18 2.3 Methods Detail 18 2.3.1 Mouse models 18 2.3.2 Adeno-Associated Virus-Mediated Gain-of-Function mPCSK9 preparation 19 2.3.3 Cultivation and infection of Trichuris muris 19 2.3.4 Cultivation and infection of Heligmosomoides polygyrus 20 2.3.5 Fecal egg Enumeration 21 2.3.6 Collection of Adult H.polygyrus Worms 21 2.3.7 Intracellular transcription factor staining 22 2.3.8 Mouse aorta digestion and FACs staining 23 2.3.9 Cholesterol E Measure 24 2.3.10 Aortic Arch Frozen section 24 2.3.11 CD68 Staining 25 2.3.12 Statistical Analysis and Significance Levels in the Study 26 Chapter 3 Result 27 3.1 Plaque formation was confirmed in mice through increased body weight and cholesterol levels 27 3.1.1 Weight gain in mice during atherosclerosis progression 27 3.1.2 Induction of atherosclerosis and plaque formation in mice using AAV-mPCSK9 27 3.2 Successful helminth infection observed in mice regardless of genotype 28 3.2.1 Detection of T. muris eggs confirms successful helminth infection in mice 28 3.2.2 Successful mouse model for studying helminth infections established 30 3.2.3 Successful colonization of H. polygyrus in mice regardless of genotype 30 3.2.4 Host-related factors drive H. polygyrus colonization independent of genotype 31 3.3 Helminth infection and dietary changes impact mouse weight and cholesterol levels 32 3.3.1 Helminth infection during the regression stage leads to a significant reduction in weight 32 3.3.2 Helminth infection and dietary switch lower mouse cholesterol levels 33 3.4 Helminth infection induces the expression of CD4 T cells, Tregs, and GATA-3 T cells in peripheral blood, contributing to the counteraction of atherosclerosis progress 34 3.4.1 Nod2-/- mice indeed induce more CD4 T cell expansion 34 3.4.2 CD4 T cells responses in Nod2-/- and WT mice during helminth infections 35 3.4.3 Treg expansion induced by helminth infection with differential effects 37 3.4.4 Inflammation and T-bet CD4 T cells in atherosclerosis progression and helminth infection 38 3.4.5 Helminth infection induces GATA-3 CD4 T cells in atherosclerosis regression stage 40 3.5 CD8 T cell increase and monocyte and macrophages accumulation in atherosclerotic plaque progression, while CD4 T cells induced during plaque regression may aid in plaque regression 42 3.5.1 The Role of CD8 and CD4 T Cell Subsets in Atherosclerosis Progression and Regression 42 3.5.2 Role of Monocytes and Macrophages in Atherosclerosis Progression and Regression 45 3.6 Distinct Immune Cell Populations in Atherosclerotic Plaque Development and Regression Revealed by UMAP Clustering 48 3.6.1 Cell cluster identification in atherosclerosis progression and regression using UMAP 48 3.7 Helminth infection promotes plaque regression in WT mice 50 3.7.1 Impact of helminth infection and genotype on atherosclerotic plaque size in mice 50 3.7.2 Infiltration of CD68 macrophages in atherosclerotic plaques 51 Chapter 4 Discussion 72 4.1 Enhancing Experimental Design 72 4.1.1 Gender Disparity in Mouse Models 72 4.1.2 Confirmation of Plaque Formation in Atherosclerosis Mouse Model 72 4.1.3 Determining the Contribution of Helminth Infection and Dietary Changes to Plaque Regression 73 4.2 Immune Cell Populations in Nod2-/- Mice and Their Response to Helminth Infection during Atherosclerosis Regression 73 4.3 Characterizing Immune Cell Populations and Macrophage Markers in Atherosclerotic Regression 75 4.4 Immunostaining and Plaque Quantification in Atherosclerosis 76 4.5 Gut-Heart Axis: Implications for Atherosclerosis and Therapeutic Strategies 77 4.6 Practical Application of Helminth Treatment for Atherosclerosis 77 Chapter 5 Conclusion 80 REFERENCE 81 | - |
| dc.language.iso | en | - |
| dc.subject | 第二型免疫反應 | zh_TW |
| dc.subject | 動脈粥狀硬化 | zh_TW |
| dc.subject | 寄生蟲 | zh_TW |
| dc.subject | 調控型T細胞 | zh_TW |
| dc.subject | Nod2-/- | zh_TW |
| dc.subject | Type 2 immunity | en |
| dc.subject | Atherosclerosis | en |
| dc.subject | Nod2-/- | en |
| dc.subject | Treg | en |
| dc.subject | Helminth | en |
| dc.title | 調節性T細胞在動脈粥狀硬化進程及逆轉過程中的作用 | zh_TW |
| dc.title | The roles of regulatory T cells in atherosclerosis progression and regression | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 楊鎧鍵;徐嘉琳;林甫容 | zh_TW |
| dc.contributor.oralexamcommittee | Kai-Chien Yang ;Chia-Lin Hsu;Fu-Jung Lin | en |
| dc.subject.keyword | 動脈粥狀硬化,寄生蟲,調控型T細胞,第二型免疫反應,Nod2-/-, | zh_TW |
| dc.subject.keyword | Atherosclerosis,Helminth,Treg,Type 2 immunity,Nod2-/-, | en |
| dc.relation.page | 88 | - |
| dc.identifier.doi | 10.6342/NTU202302645 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2023-08-04 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科技學系 | - |
| dc.date.embargo-lift | 2028-09-01 | - |
| 顯示於系所單位： | 生化科技學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-111-2.pdf 未授權公開取用 | 3.42 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。